Methanol → 2-(2-fluoro-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(5-(4'-methyl-[1,1'-biphenyl]-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)benzamido)acetic acid

HRID 923624Notes

Reaction equation

HRID 923624 reaction equation
[F:1][C:2]1[CH:40]=[C:39]([NH:41][C:42](=[O:56])[CH2:43][C:44]2[CH:49]=[CH:48][C:47]([O:50][CH3:51])=[CH:46][C:45]=2[C:52]([F:55])([F:54])[F:53])[CH:38]=[CH:37][C:3]=1[C:4]([N:6]([CH2:32][C:33]([O:35]C)=[O:34])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[N:18]=[C:17]([C:19]3[CH:24]=[CH:23][C:22]([C:25]4[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=4)=[CH:21][CH:20]=3)[O:16][N:15]=2)=[CH:10][CH:9]=1)=[O:5].CO.[Li+].[OH-]>C1COCC1>[F:1][C:2]1[CH:40]=[C:39]([NH:41][C:42](=[O:56])[CH2:43][C:44]2[CH:49]=[CH:48][C:47]([O:50][CH3:51])=[CH:46][C:45]=2[C:52]([F:55])([F:53])[F:54])[CH:38]=[CH:37][C:3]=1[C:4]([N:6]([CH2:32][C:33]([OH:35])=[O:34])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[N:18]=[C:17]([C:19]3[CH:20]=[CH:21][C:22]([C:25]4[CH:26]=[CH:27][C:28]([CH3:31])=[CH:29][CH:30]=4)=[CH:23][CH:24]=3)[O:16][N:15]=2)=[CH:10][CH:9]=1)=[O:5]

Participants

5

Reactant 3

HCID 887MethanolHCID 3939Lithium HydroxideHCID 71112503methyl 2-(2-fluoro-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(5-(4'-methyl-[1,1'-biphenyl]-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)benzamido)acetate

Product 1

HCID 711116332-(2-fluoro-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(5-(4'-methyl-[1,1'-biphenyl]-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)benzamido)acetic acidYield 28%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Prepared using General Procedure 9. To a stirring solution of methyl 2-(2-fluoro-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(5-(4′-methyl-[1,1′-biphenyl]-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)benzamido)acetate INT-79 (91 mg, 0.119 mmol) in THF (2 mL) and MeOH (0.25 mL) was added 1 M LiOH (146 μL, 0.146 mmol). The reaction mixture was stirred at room temperature for 18 h. The solvent was removed and the residue suspended in water (5 mL). The mixture was acidified to pH 1 using 1 M HCl, filtered under vacuum and the captured solid washed with MeOH (1 mL). The captured solid was triturated with diethyl ether (3 mL) to afford 25 mg (28%) of 2-(2-fluoro-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(5-(4′-methyl-[1,1′-biphenyl]-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)benzamido)acetic acid 496. LCMS-ESI (m/z) calculated for C41H32F4N4O6: 752; found 753 [M+H]+, tR=9.64 min (Method 9). 1H NMR (400 MHz, DMSO) δ 10.18 (s, 1H), 8.35-8.18 (m, 2H), 8.07 (d, J=7.8 Hz, 2H), 7.98-7.86 (m, 2H), 7.73-7.65 (m, 2H), 7.64-7.39 (m, 5H), 7.39-7.33 (m, 2H), 7.30 (d, J=8.2 Hz, 1H), 7.25-7.17 (m, 2H), 4.82 (br, 2H), 3.96-3.78 (m, 5H), 3.42 (br, 2H), 2.40 (s, 3H).

Workup

  1. customPrepared
  2. customThe solvent was removed
  3. filtrationfiltered under vacuum
  4. washthe captured solid washed with MeOH (1 mL)
  5. customThe captured solid was triturated with diethyl ether (3 mL)

Sources & evidence

ORD record
ord-2cf6ea9f58604cf1b7ecdf3f0459870b
Source dataset
uspto-grants-2016_03
Patent number
US09278910B2

Reaction notes

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